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Biomedical subjects

J D Finkelstein

Publications and source records attributed to J D Finkelstein.

At least 37 records · Page 2Linked to original sources

Inactivation of betaine-homocysteine methyltransferase by adenosylmethionine and adenosylethionine.

Preincubation of betaine-homocysteine methyltransferase, prepared from rat liver, with either S-adenosylmethionine or S-adenosylethionine results in a marked loss of enzyme activity. Gel filtration did not restore activity. However both S-adenosylhomocysteine and L-homocysteine, when added to the preincubation medium, inhibited the inactivation of betaine-homocysteine methyltransferase.

Adenosine↗

Regulation of hepatic betaine-homocysteine methyltransferase by dietary betaine.

The level of betaine-homocysteine methyltransferase increases in the livers of rats fed diets supplemented with betaine or choline. The increase occurs within 3 days following the change in diet. When we administered betaine by intraperitoneal injection to rats fed choline-free diets, we observed a similar increase within 24 hours. Since betaine-homocysteine methyltransferase catalyzes a reaction which is essential for the catabolism of betaine, these changes provide a means for adaptation to excessive levels of dietary choline and betaine.

Animals↗

Methionine metabolism in mammals: concentration of metabolites in rat tissues.

We have evaluated factors which regulate the content of methionine, adenosylmethionine, adenosylhomocysteine, cystine, cysteine and acid-soluble thiols in rat tissues. In liver the concentration of methionine appears relatively insensitive to changes in dietary protein intake. In contrast the hepatic levels of adenosylmethionine, adenosylhomocysteine, cystine, cysteine and soluble thiols increased with augmented dietary protein. The ratio of adenosylmethionine: adenosylhomocysteine approximated 6.0 in livers, brains, kidneys and skeletal muscles from rats fed the stock diet. Independent variation in the concentrations of these two metabolites did occur. However, the ratios in livers of animals maintained on diets with varying casein content equaled or exceeded a value of 5.0. We conclude that the maintenance of the concentration of methionine is the primary result of the various homeostatic mechanisms. In addition, most previous reports have overestimated the tissue content of adenosylhomocysteine.

Amino Acids, Sulfur↗

Type B hepatitis after needle-stick exposure: prevention with hepatitis B immune globulin. Final report of the Veterans Administration Cooperative Study.

Hepatitis B immune globulin (HBIG) and immune serum globulin (ISG) were examined in a randomized, double-blind trial to assess their relative efficacies in preventing type B hepatitis after needle-stick exposure to hepatitis B surface antigen (HBsAG)-positive donors. Clinical hepatitis developed in 1.4% of HBIG and in 5.9% of ISG recipients (P = 0.016), and seroconversion (anti-HBs) occurred in 5.6% and 20.7% of them respectively (P less than 0.001). Mild and transient side-effects were noted in 3.0% of ISG and in 3.2% of HBIG recipients. Available donor sera were examined for DNA polymerase (DNAP) and e antigen and antibody (HBeAg; anti-HBE). Both DNAP and HBeAg showed a highly statistically significant correlation with the infectivity of HBsAg-positive donors. Hepatitis B immune globulin remained significantly superior to ISG in preventing type B hepatitis even when the analysis was confined to these two high-risk subgroups. The efficacy of ISG in preventing type B hepatitis cannot be ascertained because a true placebo group was not included.

Adolescent↗

A randomized, double blind controlled trial of the efficacy of immune serum globulin for the prevention of post-transfusion hepatitis. A Veterans Administration cooperative study.

A double blind, randomized, controlled trial has been conducted in 11 Veterans Administration hospitals during a 49-month period to compare the relative efficacies of immune serum globulin (ISG) and an albumin placebo for the prevention of post-transfusion hepatitis (PTH). A total of 2204 patients, of whom 1094 received ISG, participated in the study. The results indicate that ISG significantly reduced the incidence of icteric type non-B hepatitis only (inferred to be also type non-A hepatitis). Adverse reactions were rare, and the ISG did not significantly alter the incubation period or duration of the disease. The data suggest, however, that a similar reduction in type non-A, non-B hepatitis would have occurred had commercial blood been excluded from use. Analysis of the 241 patients who developed hepatitis indicates that type B hepatitis constituted less than 20% of the cases each year of the study. Furthermore, the efficacy of the ISG, manufactured in 1944, against apparent type non-A, non-B hepatitis suggests that this overlooked disease has existed from at least that time. Host- and transfusion-related factors that might have modified the development of PTH were examined. The use of commercial blood was observed to be the most important risk factor. It is concluded that the PTH incidence can be most effectively reduced by eliminating commercial donor blood, and continuing to screen volunteer donors for hepatitis B surface antigen (HBsAg) by sensitive procedures. Of prime importance is the need to define the agent(s) responsible for type non-A, non-B hepatitis.

Adult↗

Efficacy of hepatitis B immune serum globulin after accidental exposure. Preliminary report of the Veterans Administration Cooperative Study.

A randomised, double-blind, controlled trial has been undertaken to compare the efficacy of hepatitis B immune globulin (H.B.I.G.) with that of immune serum globulin (I.S.G.) for the prophylaxis of viral hepatitis. Participants in the trial were individuals exposed accidentally to material infectious for hepatitis (primarily viral B hepatitis). Preliminary evaluation of the first 302 of the 561 individuals entered into the study indicates that H.B.I.G. significantly reduced the frequencies of both clinical and subclinical hepatitis during the first 3--4 months after the injection. Less than 10% of H.B.I.G. recipients had detectable anti-HBs at the sixth month after the injection, suggesting that H.B.I.G. might need to be given every 3--4 months to continually exposed individuals. Further long-term evaluation is required in order to define more clearly those most likely to benefit from H.B.I.G.

Clinical Trials as Topic↗

Folate-responsive homocystinuria and "schizophrenia". A defect in methylation due to deficient 5,10-methylenetetrahydrofolate reductase activity.

Homocystinuria and homocystinemia without hypermthioninemia, but with reccurent episodes of folate responseive schizophrenic-like behavior, was documented in a mildly retarded adolescent girl who lacked the habitus associated with cystathionine synthase deficiency. Enzymes involved in homocysteine-methionine metabolism were demonstrated to be normal. A defect in the ability to reducte N-5-10--methylenetetrahydrofolate to 5-methyltetrahydrofolate was demonstrated. Methylenetetrahydrofolate reductase was 18 per cent of control values. Methyltetrahydrofolate is used for the methylation of homocysteine to methionine, and a deficiency of this compound could explain the homocystinemia and homocystinuria.

Adolescent↗